Oncogenesis is one of the recognized late effects of successful cancer therapy. Radiation therapy has been implicated in most cases to date. Some anti-cancer chemotherapeutic agents also are carcinogenic. The combination of the two could lead to an increase in the frequency of second malignant neoplasms (SMNs). A clinical study, mounted to investigate this possibility, determined that the risk of developing an SMN in an irradiated field was reduced by a factor of seven in children receiving actinomycin D (AMD). The laboratory study proposed is designed to determine whether AMD affords "protection" against RT-associated malignant tumors in laboratory animals. The study is divided into three phases: a suitable laboratory model will be developed during Phase I. Phase II will test whether AMD affords protection against RT-associated tumors, and Phase III will determine whether AMD is unique and specific in altering radiation oncogenesis. If confirmed in the laboratory, the effect might have clinical usefulness in protecting patients at high risk for developing cancer, whether related to radiation or not. It can also be used as a "probe" for the better understanding of oncogenesis; at least, radiation oncogenesis.